The underlying hypothesis in this proposal is that Computed Tomography could be significantly augmented with the addition of near-infrared spectral imaging capabilities which are more sensitive to the structure and function of cancer tissues, and that improved understanding and development of cancer therapies will then be possible. The practical tests of this overarching hypothesis are focused on the development of a novel pre-clinical imaging system for tumor diagnosis and monitoring in cancer therapy. A small animal x-ray Computed Tomography (microCT) with Near-Infrared (NIR) tomography system will be combined. This microCT/NIR system will be the only system of its kind in the world, and will allow high resolution imaging of soft tissue volumes and quantification of hemoglobin, oxygen saturation, water and exogenous molecular tracers, with CT-guided image reconstruction. The study will evaluate the optimal coupling of NIR tomography into the CT, including contact and non-contact based systems. The study will test broadband spectral tomography to provide the maximal information possible and utilize reconstruction from non-contact data which is insensitive to boundary errors in the model-based image reconstruction procedure. The completed system will be used in studies of tumor damage induced by vascular and cellular directed therapies. The system will be developed in a unique academic-industry partnership with Imtek Inc, as well as with institutional support and with partnership from the NCI Network for Translational Research in Optical Imaging (NTROI). This system is specifically being designed following the innovations in CT-PET imaging that can be done with the same system, but in this application we will exploit the capabilities for NIR imaging to provide functional tissue information. The CT information is implemented as a soft prior information which can be utilized for constraint or initial prior information. The system will be evaluated with subcutaneous and orthotopic prostate cancer tumors which have well characterized vascular densities and oxygen histograms. The system will be used to define the maximal signal changes in terms of contrast to noise, which are quantitative signatures of therapeutic change. The culmination of this work will see the a working version of a one of a kind tomography system, and pave the way for future human studies, and be used in spontaneous animal studies to find and follow tumor growth which would otherwise be undetectable.